SPECIFIC AIMS Neonatal abstinence syndrome (NAS) is an opioid withdrawal syndrome that develops shortly after birth to in utero-exposed neonates. The cost of NAS is high: newborns with NAS are typically receive care in the Neonatal Intensive Care Unit (NICU), where the daily cost of care is high. Nearly 22,000 infants are born with NAS each year at a cost of $1.5 billion1. Moreover, medication-based interventions for the treatment of NAS, used in up to 80% of opioid-exposed infants, carry their own risks of toxicity and drug interactions2. Despite the medical cost, high societal impact of NAS, and the risks of treatment, the tools to assess the severity of NAS can be subjective and suffer from examiner bias3. There is an urgent need for innovative new methods to diagnose NAS and assess the efficacy of responses to treatment. Flexible, low-cost wearable devices (worn on the skin) that can report measures of systemic biochemical and biomechanical processes offer a simple and economical solution. In NAS, surges of sympathetic nervous system activity produce increased heart rate, skin conductance, unstable temperature, and tremor. These manifest in increased infant sweating, seizures, tremors, unstable body temperature, and more?events that must continually monitored and assessed by nurses. The unsupervised, objective detection/quantification of the bodily response of neonates suffering from NAS could drive the development of new, objective scoring tools that can guide the initiation, intensity, and duration of therapies for NAS2. Such tools could significantly reduce medical costs and improve patient outcomes by reducing patient time in NICU, reducing nurse load, improving outpatient monitoring, and helping to assist in the optimization of patient treatments. Critically, we believe such a tool may be able to objectively capture events that may go unnoticed by nurses or while the infant is sleeping (minor tremors, poor oxygenation, temperature fluctuations, dehydration). This proposal seeks to develop interlinked, infant-targeted wearable biosensor-systems capable of continuously monitoring the biochemical to biophysical parameters of opioid-dependent neonates under treatment for NAS. Our team has outstanding experience in all areas necessary to this investigation. Our business unit has extensive NIH funded experience in wearable biosensing, in the detection of sympathetic nervous system activity in opioid withdrawal, pediatrics, business development, and intellectual property. Our academic partners have broad experience in novel biosensor development.